Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes
| العنوان: | Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes |
|---|---|
| المؤلفون: | Xiaohang Li, Pieter Muntendam, Carlos José Pirola, Silvia Cristina Sookoian, Neal Gordon, Paul Courchesne, Caroline S. Fox, Aram Adourian, Brian H. Chen, Peter Juhasz, Martin G. Larson, Daniel Levy, Valentin Fuster, Subha Subramanian, Christine M. Willinger, Christopher J. O'Donnell, Xiaoyan Yin, Shih-Jen Hwang, George Chen, Ivana Bobeldijk-Pastorova |
| المصدر: | The Journal of clinical endocrinology and metabolism, 6, 101, 1779-1789 CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| بيانات النشر: | Endocrine Society, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Biomedical Innovation, Medicina Clínica, Biochemistry, 0302 clinical medicine, Endocrinology, Framingham Heart Study, Life, Risk Factors, purl.org/becyt/ford/3.2 [https], DIABETES, skin and connective tissue diseases, METABOLIC SYNDROME, Middle Aged, Metabolome, Female, purl.org/becyt/ford/3 [https], Medicina Critica y de Emergencia, MHR - Metabolic Health Research, Healthy Living, Adult, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, BIOMARKERS, 030209 endocrinology & metabolism, Context (language use), Biology, METABOLOMICS, Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, Diabetes mellitus, Internal medicine, medicine, Humans, Metabolomics, Obesity, Risk factor, Aged, Dyslipidemias, Biochemistry (medical), Original Articles, medicine.disease, 030104 developmental biology, sense organs, ELSS - Earth, Life and Social Sciences, Metabolic syndrome, Body mass index, Dyslipidemia |
| الوصف: | CONTEXT: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia. OBJECTIVE: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor changes over time. DESIGN: Cross-sectional—discovery samples (n = 650; age, 36–69 years) from the Framingham Heart Study (FHS) and replication samples (n = 670; age, 61–76 years) from the BioImage Study, both following a factorial design sampled from high vs low strata of body mass index, lipids, and glucose. Longitudinal—FHS participants (n = 554) with 5–7 years of follow-up for risk factor changes. SETTING: Observational studies. PARTICIPANTS: Cross-sectional samples with or without obesity, dysglycemia, and dyslipidemia, excluding prevalent cardiovascular disease and diabetes or dyslipidemia treatment. Age- and sex-matched by group. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Gas chromatography-mass spectrometry detected 119 plasma metabolites. Cross-sectional associations with obesity, dyslipidemia, and dysglycemia were tested in discovery, with external replication of 37 metabolites. Single- and multi-metabolite markers were tested for association with longitudinal changes in risk factors. RESULTS: Cross-sectional metabolite associations were identified with obesity (n = 26), dyslipidemia (n = 21), and dysglycemia (n = 11) in discovery. Glutamic acid, lactic acid, and sitosterol associated with all three risk factors in meta-analysis (P < 4.5 × 10−4). Metabolites associated with longitudinal risk factor changes were enriched for bioactive lipids. Multi-metabolite panels explained 2.5–15.3% of longitudinal changes in metabolic traits. CONCLUSIONS: Cross-sectional results implicated dysregulated glutamate cycling and amino acid metabolism in metabolic risk. Certain bioactive lipids were associated with risk factors cross-sectionally and over time, suggesting their upstream role in risk factor progression. Functional studies are needed to validate findings and facilitate translation into treatments or preventive measures. Fil: Yin, Xiaoyan. Framingham Heart Study; Estados Unidos. Boston University; Estados Unidos Fil: Subramanian, Subha. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Willinger, Christine M.. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Chen, George. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Juhasz, Peter. BG Medicine; Estados Unidos Fil: Courchesne, Paul. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Chen, Brian H.. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Li, Xiaohang. BG Medicine; Estados Unidos Fil: Hwang, Shih Jen. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos Fil: Fox, Caroline S.. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos. Brigham and Women’s Hospital. Department of Medicine; Estados Unidos. Harvard Medical School; Estados Unidos Fil: O'Donnell, Christopher J.. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos. Massachusetts General Hospital. Department of Medicine; Estados Unidos. Harvard Medical School; Estados Unidos Fil: Muntendam, Pieter. BG Medicine; Estados Unidos Fil: Fuster, Valentin. Mt. Sinai School of Medicine; Estados Unidos. Centro Nacional de Investigaciones Cardiovasculares; España. Cedars Sinai Medical Center; Estados Unidos Fil: Bobeldijk Pastorova, Ivana. TNO Triskelion BV; Países Bajos Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Gordon, Neal. BG Medicine; Estados Unidos Fil: Adourian, Aram. BG Medicine; Estados Unidos Fil: Larson, Martin G.. Framingham Heart Study; Estados Unidos. Boston University; Estados Unidos Fil: Levy, Daniel. Framingham Heart Study; Estados Unidos. National Institutes of Health; Estados Unidos. Boston University; Estados Unidos |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8684997aa09841b34caa3ad0651d0dbTest https://academic.oup.com/jcem/article/101/4/1779/2804590Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b8684997aa09841b34caa3ad0651d0db |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |